Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma
The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma and B16 melanoma, was stromal cells. In the pres...
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| Format: | Article |
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Frontiers Media S.A.
2015-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00332/full |
| _version_ | 1819057577845063680 |
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| author | Teizo eYoshimura Mingyong eLiu Mingyong eLiu Xin eChen Xin eChen Liangzhu eLi Liangzhu eLi Ji Ming eWang |
| author_facet | Teizo eYoshimura Mingyong eLiu Mingyong eLiu Xin eChen Xin eChen Liangzhu eLi Liangzhu eLi Ji Ming eWang |
| author_sort | Teizo eYoshimura |
| collection | DOAJ |
| description | The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both WT and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1. |
| first_indexed | 2024-12-21T13:41:32Z |
| format | Article |
| id | doaj.art-acabe398a6df4382889ad8c286646af9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T13:41:32Z |
| publishDate | 2015-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-acabe398a6df4382889ad8c286646af92022-12-21T19:01:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-06-01610.3389/fimmu.2015.00332146473Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung CarcinomaTeizo eYoshimura0Mingyong eLiu1Mingyong eLiu2Xin eChen3Xin eChen4Liangzhu eLi5Liangzhu eLi6Ji Ming eWang7National Cancer InstituteDaping Hospital, Third Military Medical UniversityNational Cancer InstituteUniversity of MacauLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer ResearchEngineering Research Center for Cell and Therapeutic Antibody of Ministry of Education, School of Pharmacy, Shanghai Jiaotong UniversityNational Cancer InstituteNational Cancer InstituteThe chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both WT and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00332/fullChemokinesInflammationTumor Microenvironmentlung cancermonocytes/macrophages |
| spellingShingle | Teizo eYoshimura Mingyong eLiu Mingyong eLiu Xin eChen Xin eChen Liangzhu eLi Liangzhu eLi Ji Ming eWang Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma Frontiers in Immunology Chemokines Inflammation Tumor Microenvironment lung cancer monocytes/macrophages |
| title | Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma |
| title_full | Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma |
| title_fullStr | Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma |
| title_full_unstemmed | Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma |
| title_short | Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma |
| title_sort | crosstalk between tumor cells and macrophages in stroma renders tumor cells as the primary source of mcp 1 ccl2 in lewis lung carcinoma |
| topic | Chemokines Inflammation Tumor Microenvironment lung cancer monocytes/macrophages |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00332/full |
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